Purpose: We used bioinformatics methods and Mendelian randomization (MR) analysis to investigate the hub genes involved in acute myeloid leukemia (AML) and their causal relationship with hemolysis, to explore a new direction for molecular biology research of AML. Methods: We first differentially analyzed peripheral blood samples from 62 healthy volunteers and 65 patients with AML from the Gene Expression Omnibus database to obtain differentially expressed genes (DEGs), and intersected them with genes sourced from weighted gene co-expression network analysis (WGCNA) and the GeneCards database to obtain target genes. Target genes were screened using protein–protein interaction (PPI) network analysis and ROC curves to identify genes associated with AML. Finally, we analyzed the correlation between genes and immune cells and the relationship between toll-like receptor 4 (TLR4) and AML using MR. Results: We compared peripheral blood expression profiles using an array of 62 healthy volunteers (GSE164191) and 65 patients with AML (GSE89565) (M0:25; M1:11; M2:10; M3:1; M4:7; M4 eo t [16;16] ou inv [16]:4; M5:6; M6:1) and obtained 7,339 DEGs (3,733 upregulated and 3,606 downregulated). We intersected these DEGs with 4,724 genes from WGCNA and 1,330 genes related to hemolysis that were identified in the GeneCards database to obtain 190 target genes. After further screening these genes using the PPI network, we identified TLR4, PTPRC, FCGR3B, STAT1, and APOE, which are closely associated with hemolysis in patients with AML. Finally, we found a causal relationship between TLR4 and AML occurrence using MR analysis (p < 0.05). Conclusion We constructed a WGCNA-based co-expression network and identified hemolysis-associated AML genes.

Purpose: We used bioinformatics methods and Mendelian randomization (MR) analysis to investigate the hub genes involved in acute myeloid leukemia (AML) and their causal relationship with hemolysis, to explore a new direction for molecular biology research of AML. Methods: We first differentially analyzed peripheral blood samples from 62 healthy volunteers and 65 patients with AML from the Gene Expression Omnibus database to obtain differentially expressed genes (DEGs), and intersected them with genes sourced from weighted gene co-expression network analysis (WGCNA) and the GeneCards database to obtain target genes. Target genes were screened using protein–protein interaction (PPI) network analysis and ROC curves to identify genes associated with AML. Finally, we analyzed the correlation between genes and immune cells and the relationship between toll-like receptor 4 (TLR4) and AML using MR. Results: We compared peripheral blood expression profiles using an array of 62 healthy volunteers (GSE164191) and 65 patients with AML (GSE89565) (M0:25; M1:11; M2:10; M3:1; M4:7; M4 eo t [16;16] ou inv [16]:4; M5:6; M6:1) and obtained 7,339 DEGs (3,733 upregulated and 3,606 downregulated). We intersected these DEGs with 4,724 genes from WGCNA and 1,330 genes related to hemolysis that were identified in the GeneCards database to obtain 190 target genes. After further screening these genes using the PPI network, we identified TLR4, PTPRC, FCGR3B, STAT1, and APOE, which are closely associated with hemolysis in patients with AML. Finally, we found a causal relationship between TLR4 and AML occurrence using MR analysis (p < 0.05). Conclusion We constructed a WGCNA-based co-expression network and identified hemolysis-associated AML genes.

Purpose: We used bioinformatics methods and Mendelian randomization (MR) analysis to investigate the hub genes involved in acute myeloid leukemia (AML) and their causal relationship with hemolysis, to explore a new direction for molecular biology research of AML. Methods: We first differentially analyzed peripheral blood samples from 62 healthy volunteers and 65 patients with AML from the Gene Expression Omnibus database to obtain differentially expressed genes (DEGs), and intersected them with genes sourced from weighted gene co-expression network analysis (WGCNA) and the GeneCards database to obtain target genes. Target genes were screened using protein–protein interaction (PPI) network analysis and ROC curves to identify genes associated with AML. Finally, we analyzed the correlation between genes and immune cells and the relationship between toll-like receptor 4 (TLR4) and AML using MR. Results: We compared peripheral blood expression profiles using an array of 62 healthy volunteers (GSE164191) and 65 patients with AML (GSE89565) (M0:25; M1:11; M2:10; M3:1; M4:7; M4 eo t [16;16] ou inv [16]:4; M5:6; M6:1) and obtained 7,339 DEGs (3,733 upregulated and 3,606 downregulated). We intersected these DEGs with 4,724 genes from WGCNA and 1,330 genes related to hemolysis that were identified in the GeneCards database to obtain 190 target genes. After further screening these genes using the PPI network, we identified TLR4, PTPRC, FCGR3B, STAT1, and APOE, which are closely associated with hemolysis in patients with AML. Finally, we found a causal relationship between TLR4 and AML occurrence using MR analysis (p < 0.05). Conclusion We constructed a WGCNA-based co-expression network and identified hemolysis-associated AML genes.

The aim of this study was to prepare a self-assembled nanoparticle monkeypox vaccine candidate and study its immune response characteristics,so as to provide reference test data for its vaccine design.The antigen protein A29L-SpyTag and the backbone protein Mi3-SpyCatcher were expressed and purified by prokaryotic system,and nanoparticles A29L-Mi3 were prepared by chemical assembly,then the antibody titers were determined by ELISA,the antibody neutralization was determined by plaque test,and the cytokine secretion of lymphocytes was determined by flow cytometry to describe the immune response characteristics.Data showed that A29L-Mi3 nanoparticles were successfully prepared,and the particles were uniformly distributed in hollow cages,with an average particle size of(29±0.19)nm.After the A29L-Mi3 nanoparticle vaccine candidate was combined with SP01 adjuvant,the neutralizing antibody titer was stronger than that of the A29L protein candidate,and the A29L-Mi3 nanoparticle vaccine candidate could obtain neutralizing antibodies with similar titers after two immunizations.The level of mouse T lymphocyte immune response activated by the A29L-Mi3 nanoparticle vaccine candidate was higher than that of the A29L protein vaccine candidate.In conclusion,A29L-Mi3 protein nanoparticles with uniform structure have successfully assembled in vitro,which has strong immunogenicity and improved neutralization ability after combination with SP01 adjuvant,thus provided reference data for the optimization of immune programs.In addition,the level of cellular immune response is higher than that of A29L protein alone,which provides a reference for the design and development of monkeypox vaccine.

There is still a lack of experience in the perioperative strategy for esophageal cancer patients in China during the epidemic of COVID-19. In December 2022, a 59-year-old male patient with esophageal cancer was admitted to our department. He received 2 cycles of neoadjuvant therapy before surgery, and developed COVID-19 perioperatively. After treatment, the infection symptoms of the patient were improved, and the postoperative recovery was satisfactory.

Objective To summarize the treatment of cervical cancer patients diagnosed before 34 weeks of gestation who chose to continue pregnancy,and to provide clinical experience for improving maternal and fetal outcomes.Methods Clinical data of pregnant women with cervical cancer admitted to the Obstetrics and Gynecology Hospital,Fudan University from Jan 2013 to Feb 2024 were collected and analyzed.Treatment of patients diagnosed before 34 weeks of gestation and chose to continue pregnancy was summarized.Outcomes of patients and newborn were followed up.Results A total of 15 patients were enrolled with a median age of 34 years old.Nine cases(9/15)represented clinical symptom of abnormal vaginal bleeding,14 cases(14/15)of patients were diagnosed in the middle or late stages of pregnancy,12 cases(12/15)diagnosed with tumor size of more than 2 cm,13 patients(13/15)infected HPV type 16 or 18.The main pathological type was squamous cell carcinoma(9/15).Regarding therapy,one patient with stage Ⅰa1 was under observation and underwent a caesarean section and total hysterectomy at 35 weeks of gestation due to premature rupture of membrane and a scarred uterus.For the other patients with 14 stage Ⅰb,lymph node metastasis was excluded by pelvic lymphadenectomy or MRI,and then neoadjuvant chemotherapy was administered.Termination of pregnancy and standardized treatment for cervical cancer were provided after 34 weeks of gestation.One patient's pathology was upgraded to stage Ⅱa1 after surgery.Up to follow-up,13 out of 15 patients had survived without tumors.The average gestational age of newborns was(35.0±1.5)weeks,and the average birth weight was(2 345.33±431.44)g.Blood tests conducted one day after delivery of the newborns revealed that:8 newborns(8/15)had hypoleukocyte and one newborn(1/15)had anemia.After short-term hospitalization and supportive treatment,all newborns'progress was favorable.Conclusion For pregnant patients with stage Ⅰb cervical cancer diagnosed before 34 weeks of gestation,postponing termination to after 34 weeks of gestation through neoadjuvant chemotherapy and then giving standardized treatment for cervical cancer was safe with favorable maternal and fetal prognosis.

Objective:To explore the risk factors affecting the survival and efficacy of patients with acute myeloid leukemia with myelodysplasia-related changes(AML-MRC)transformed from myelodysplastic syndrome(MDS).Methods:The clinical data of 60 patients with AML-MRC transformed from MDS who hospitalized in The Third Affiliated Hospital of Soochow University from January 2010 to December 2021 were retrospectively analyzed.The demographic data and laboratory parameters,cytogenetic karyotypes,target genes of AML detected by next generation sequence,risk stratification,treatment regimen,therapeutic efficacy and survival outcome were documented.Rank sum test and Chi-square test or Fisher exact test were used to compare the survival and efficacy.The effects of clinical parameters,risk stratification and treatment regimens on the survival and efficacy of the AML-MRC patients were analyzed by univariate and multivariate analysis.Results:The median overall survival(OS)of the AML-MRC patients was 4.5 months,the 1-year OS rate was 28.3％,and the complete remission(CR)rate after treatment was 33.3％.The univariate analysis showed that age≥60 years,leukocytosis,severe thrombocytopenia,poor-risk group and only accepted hypomethylating agents(HMAs)or supportive therapy were the risk factors affecting OS.COX multivariate analysis showed that thrombocytopenia(HR=4.46),HMAs therapy(compared to transplantation,HR=10.47),supportive therapy(compared to transplantation,HR=25.80)and poor-risk group(compared to medium-risk group,HR=13.86)were independent hazard factors for median OS of patients with AML-MRC.The univariate analysis showed that the risk factors affecting 1-year OS in patients with AML-MRC were age ≥ 60 years,thrombocytopenia,time of transformation from MDS to AML(TTA)≥3 months,fibrinogen-albumin ratio index(FARI)≥ 0.07,CONUT score≥5,poor-risk group and supportive therapy.Binary logistic regression analysis showed that the independent risk factors for 1-year OS in AML-MRC patients were age ≥ 60 years(HR=11.23),thrombocytopenia(HR=8.71),FARI ≥ 0.07(HR=5.19)and poor-risk group(HR=14.00).The risk factors affecting CR of AML-MRC patients in univariate analysis were age ≥ 60 years,thrombocytopenia,FARI ≥ 0.1,CONUT score ≥ 5,poor-risk group and supportive therapy,while binary logistic regression analysis showed that age ≥ 60 years(HR=7.35),CONUT score ≥ 5(HR=9.60),thrombocytopenia(HR=12.05)and poor-risk group(HR=32.5)were independent risk factors affecting CR of the patients.Conclusion:The OS of AML-MRC patients is poor,old age(≥ 60 years old),supportive therapy,HMA therapy,poor-risk,thrombocytopenia,FARI ≥ 0.07 and CONUT score ≥ 5 may be associated with poor prognosis.

Objective:To discuss the association between occupational acid fog exposure and accelerated biological aging of the workers,and to clarify its related risk factors.Methods:A total of 341 male workers exposed to occupational acid fog and 201 male workers without occupational exposure were selected as the study subjects,and they were divided into exposure group and control group,respectively.The general informations of the subjects in two groups were collected through questionnaires and physical examinations.The levels of red blood cell count(RBC),platelet count(PLT),albumin(ALB),urea(Urea),creatinine(CR),triglycerides(TG),total cholesterol(TC),glycated hemoglobin(HBA1c),and high-sensitivity C-reactive protein(Hs-CRP)in serum of the subjects in two groups were detected.The Klemera-Doubal method(KDM)was used to construct the composite aging measure,KDM-biological age(BA)(KDM-BA).The model parameters were trained using samples from the 2009 China Health and Nutrition Survey(CHNS)Database to calculate the BA acceleration of the subjects in two groups;stratified analysis based on the population characteristics was conducted to analyze the BA of the subjects in two groups with different population characteristics;generalized linear model was used to analyze the factors influencing BA acceleration due to acid fog exposure.Results:The model parameters were trained using samples from the 2009 CHNS Database,including 8 133 cases aged 20-79 years,of which 3 788 were male.The levels of Urea,CR,HBA1c,ALB,and TC,as well as systolic blood pressure(SBP),total working years,sleep duration,and body mass index(BMI)of the subjects between two groups had significant differences(P<0.05).Compared with control group,the BA acceleration of the subjects in exposure group was significantly increased(P<0.05).In entire population and exposure group,the BA acceleration in the smokers was significantly higher than that in the non-smokers(P<0.05).In entire population,control group,and exposure group,the BA accelerations of the subjects in different BMI groups were significantly decreased with the increase of BMI(P<0.05).Compared with control group,the BA acceleration of the subjects in exposure group was significantly increased(P<0.05),including those under 40 years old,with total working years of 4-7 years,Han nationality,unmarried,smokers,and sleep duration 6-7 h,and with overweight.Acid fog exposure,smoking,and BMI were associated with the BA acceleration(β=0.72,95%CI:0.24-1.21;β=0.59,95%CI:0.11-1.06;β=-0.29,95%CI:-0.35—-0.22).Conclusion:Occupational acid fog exposure may accelerate the biological aging in the workers,and acid fog is a risk factor to accelerate the biological aging of the body.

To analyze the factors associated with infection and death of carbapenem-resistant Klebsiella pneumoniae (CRKP) in patients. Using a case-control study method, patients with CRKP infection from January 2019 to December 2021 in the 3201 Hospital were selected as the case group, and patients with carbapenem-susceptible Klebsiella pneumoniae (CSKP) infection in the same period were selected as the control group in a ratio of 1∶1. The study subjects were followed up for 30 days. The two groups of patients were categorized into survival and death groups based on whether they died or not, respectively, and the 30-day morbidity and mortality rates of the CRKP case group and the CSKP control group were compared. The logistic regression model was used to analyze the factors associated with CRKP infection and death after CRKP infection. This study included 59 cases in the CRKP case group and 59 in the CSKP control group. The 30-day mortality rate of CRKP-infected patients and CSKP-infected patients were 30.5% (18/59) and 5.1% (3/59), with statistically significant differences ( P<0.001). Surgery within three months prior to KP infection ( OR=17.285, P=0.001), use of carbapenems within three months prior to KP infection ( OR=11.235, P=0.002), use of more than three types of antibiotics ( OR=7.993, P=0.016), albumin<30 g/L in patients prior to KP infection ( OR=10.463, P=0.002), sex ( OR=0.078, P<0.001), and diabetes ( OR=0.076, P=0.011) were associated factors of CRKP infection. Higher age-corrected Charlson Comorbidity Index scores of patients ( OR=1.522, P=0.024) and use of carbapenems by the patients with in the first three months prior to the KP infection ( OR=4.902, P=0.029) were associated factors for the deaths of patients with CRKP. In conclusion, medical personnel should be cautious in performing invasive procedures, strictly control the use of antibiotics, and provide targeted protection and treatment for high-risk patients as soon as possible.

Digital intraoral scanning is a hot topic in the field of oral digital technology.In recent years,digital intra-oral scanning has gradually become the mainstream technology in orthodontics,prosthodontics,and implant dentistry.The precision of digital intraoral scanning and the accuracy and stitching of data collection are the keys to the success of the impression.However,the operators are less familiar with the intraoral scanning characteristics,imaging process-ing,operator scanning method,oral tissue specificity of the scanned object,and restoration design.Thus far,no unified standard and consensus on digital intraoral scanning technology has been achieved at home or abroad.To deal with the problems encountered in oral scanning and improve the quality of digital scanning,we collected common expert opin-ions and sought to expound the causes of scanning errors and countermeasures by summarizing the existing evidence.We also describe the scanning strategies under different oral impression requirements.The expert consensus is that due to various factors affecting the accuracy of digital intraoral scanning and the reproducibility of scanned images,adopting the correct scanning trajectory can shorten clinical operation time and improve scanning accuracy.The scanning trajec-tories mainly include the E-shaped,segmented,and S-shaped methods.When performing fixed denture restoration,it is recommended to first scan the abutment and adjacent teeth.When performing fixed denture restoration,it is recommend-ed to scan the abutment and adjacent teeth first.Then the cavity in the abutment area is excavated.Lastly,the cavity gap was scanned after completing the abutment preparation.This method not only meets clinical needs but also achieves the most reliable accuracy.When performing full denture restoration in edentulous jaws,setting markers on the mucosal tissue at the bottom of the alveolar ridge,simultaneously capturing images of the vestibular area,using different types of scanning paths such as Z-shaped,S-shaped,buccal-palatal and palatal-buccal pathways,segmented scanning of dental arches,and other strategies can reduce scanning errors and improve image stitching and overlap.For implant restora-tion,when a single crown restoration is supported by implants and a small span upper structure restoration,it is recom-mended to first pre-scan the required dental arch.Then the cavity in the abutment area is excavated.Lastly,scanning the cavity gap after installing the implant scanning rod.When repairing a bone level implant crown,an improved indi-rect scanning method can be used.The scanning process includes three steps:First,the temporary restoration,adjacent teeth,and gingival tissue in the mouth are scanned;second,the entire dental arch is scanned after installing a standard scanning rod on the implant;and third,the temporary restoration outside the mouth is scanned to obtain the three-di-mensional shape of the gingival contour of the implant neck,thereby increasing the stability of soft tissue scanning around the implant and improving scanning restoration.For dental implant fixed bridge repair with missing teeth,the mobility of the mucosa increases the difficulty of scanning,making it difficult for scanners to distinguish scanning rods of the same shape and size,which can easily cause image stacking errors.Higher accuracy of digital implant impres-sions can be achieved by changing the geometric shape of the scanning rods to change the optical curvature radius.The consensus confirms that as the range of scanned dental arches and the number of data concatenations increases,the scanning accuracy decreases accordingly,especially when performing full mouth implant restoration impressions.The difficulty of image stitching processing can easily be increased by the presence of unstable and uneven mucosal mor-phology inside the mouth and the lack of relatively obvious and fixed reference objects,which results in insufficient ac-curacy.When designing restorations of this type,it is advisable to carefully choose digital intraoral scanning methods to obtain model data.It is not recommended to use digital impressions when there are more than five missing teeth.